NTB-A, a single-pass type I membrane glycoprotein also referred to as SLAMF6, is an immunoglobulin superfamily (Ig-SF) member belonging to the CD2/SLAM subfamily. See, e.g., Bottino et al., J. Exp. Med. 194:235-246, 2001. NTB-A is characterized, in its extracellular portion, by an N-terminal V-type domain followed by a C2-type domain, while the intracytoplasmic portion contains three tyrosine-based motifs: two immunoreceptor tyrosine-based switch motifs (ITSM; TxYxxV/I) and a classical immunoreceptor tyrosine-based inhibition motif (ITIM; I/V/L/SxYxxL). See id. Through its ITSM motifs, NTB-A associates with the SH2 domain of the SLAM-associated protein SH2D1A and the related Ewing's sarcoma activated transcript (EAT) 2. See Bottino et al., supra; Falco et al., Eur. J. Immunol. 34:1663-1672, 2004; Flaig et al., J. Immunol. 172:6524-6527, 2004.
NTB-A is expressed on natural killer (NK) cells, NK-like T-cells, T-cells, monocytes, dendritic cells, B-cells, and eosinophils. See Salort JD. et al., Immunology Letters 129-136, 2011; Matesanz-Isabel et al., Immunology Letters 104-112, 2011; Munitz et al., Journal of Immunology 174:110-118, 2005; Bottino et al., Journal of Experimental Medicine 194(3):235-246; 2001. NTB-A can function through homotypic interactions (i.e., as a self-ligand), and has been shown to act as a positive regulator of NK cell functions via signaling, inducing NK cell cytotoxicity. See, e.g., See Bottino et al., supra; Falco et al., supra; Flaig et al., supra. NTB-A has also been shown to be expressed on B-cells from chronic lymphocytic leukemia (CLL) and B-cell lymphoma patients. See Korver et al., British Journal of Haematology 137:307-318, 2007.